The single cysteine on the α-subunit of bovine brain S-100a protein has been modified with the thiol specific probe, Acrylodan. When the labelled apoprotein was excited at 380 nm the fluorescence ...emission maximum was centered at 484 ± 2 nm, suggesting that the probe is in a fairly hydrophobic environment. Addition of Ca2+ to the protein caused the emission maximum to undergo a red shift to 504 ± 2 nm, implying that the fluorophore is now more exposed to the solvent. Zn2+, when added to the protein, induced only a small perturbation and the emission maximum shifted to 481 ± 2 nm. Ca2+ was able to perturb the fluorophore in the presence of Zn2+. 2-p-Toluidinylnaphthalene-6-sulfonate (TNS)-labelled α-subunit when excited at 345 nm exhibited very little fluorescence in the absence of Ca2+. Addition of Ca2+ resulted in an increase in TNS fluorescence accompanied by a blue shift of the emission maximum to 445 ± 1 nm indicating that the probe in the presence of Ca2+ moves to a hydrophobic domain. The fact that Ca2+ and Zn2+ can perturb the labelled sulfhydryl group in the presence of each other clearly demonstrates that the binding sites for the two metal ions must be different on the α-subunit as well as on the S-100a protein.
Background Proactive infection control management is crucial in preventing the introduction of multiple drug resistant organisms in the healthcare setting. In Hong Kong, where vancomycin-resistant ...enterococci (VRE) endemicity is not yet established, contact tracing and screening, together with other infection control measures are essential in limiting intra- and inter-hospital transmission. The objective of this study was to illustrate the control measures used to eradicate a VRE outbreak in a hospital network in Hong Kong. Methods We described an outbreak of VRE in a healthcare region in Hong Kong, involving a University affiliated hospital and a convalescent hospital of 1600 and 550 beds respectively. Computer-assisted analysis was utilized to facilitate contact tracing, followed by VRE screening using chromogenic agar. Multi-locus sequence typing (MLST) was performed to assess the clonality of the VRE strains isolated. A case-control study was conducted to identify the risk factors for nosocomial acquisition of VRE. Results Between November 26 and December 17, 2011, 11 patients (1 exogenous case and 10 secondary cases) in two hospitals with VRE colonization were detected during our outbreak investigation and screening for 361 contact patients, resulting in a clinical attack rate of 2.8% (10/361). There were 8 males and 3 females with a median age of 78 years (range, 40-87 years). MLST confirmed sequence type ST414 in all isolates. Case-control analysis demonstrated that VRE positive cases had a significantly longer cumulative length of stay (P 〈0.001), a higher proportion with chronic cerebral and cardiopulmonary conditions (P=0.001), underlying malignancies (P 〈0.001), and presence of urinary catheter (P 〈0.001), wound or ulcer (P 〈0.001), and a greater proportion of these patients were receiving β-lactam/ β-1actamase inhibitors (P=0.009), carbapenem group (P 〈0.001), fluoroquinolones (P=0.003), or vancomycin (P=0.001) when compared with the controls. Conclusion Extensive contact tracing and screening with a "search-and-confine" strategy was a successful tool for outbreak control in our healthcare reqion.
The sequence of the 224 residues of HMG 1 suggests it consists of three domains. We have previously proposed Cary et al. (1980 Eur. J. Biochem. 131, 367–374 that the A and B domains can fold ...autonomously and that there is also a small N domain. Several proteases are now found to cut at the end of the B domain (at or close to residue 184). It is shown that the A+B‐domain fragment also folds and probably contains all the helix of intact HMG 1. The stability of the B domain is enhanced by the presence of the A domain. The acidic C domain undergoes a coil → helix transition on lowering the pH. Several peptides have been prepared by cleavage at tryptophan. Peptide 57–C‐terminus contains complete B and C domains but does not fold. In the absence of the A domain the C domain is thus able to destabilise the B domain. It is concluded that the stability of the B domain in HMG 1 is due to interaction with the A domain and the C domain has a separate function from the other domains.
The sequence of the 224 residues of HMG 1 suggests it consists of three domains. We have previously proposed Cary et al. (1980 Eur. J. Biochem. 131, 367-374 that the A and B domains can fold ...autonomously and that there is also a small N domain. Several proteases are now found to cut at the end of the B domain (at or close to residue 184). It is shown that the A + B-domain fragment also folds and probably contains all the helix of intact HMG 1. The stability of the B domain is enhanced by the presence of the A domain. The acidic C domain undergoes a coil---helix transition on lowering the pH. Several peptides have been prepared by cleavage at tryptophan. Peptide 57--C-terminus contains complete B and C domains but does not fold. In the absence of the A domain the C domain is thus able to destabilise the B domain. It is concluded that the stability of the B domain in HMG 1 is due to interaction with the A domain and the C domain has a separate function from the other domains.
Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures ...across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.
Thriving in increasingly complex and ambiguous environments requires creativity and the capability to reconcile conflicting demands. Recent evidence with Western samples has suggested that ...paradoxical frames, or mental templates that encourage individuals to recognize and embrace contradictions, could produce creative benefits. We extended the timely, but understudied, topic by studying the nuances of for whom and why creative advantages of paradoxical frames emerge. We suggest that people endorsing a middle ground approach are less likely to scrutinize conflict and reconcile with integrative solutions, thus receiving less creative benefits of paradoxical frames. Five studies that examined individual and cultural differences in middle ground endorsement support our theory. Study 1 found that paradoxical frames increased creativity, but failed to replicate that experienced conflict mediated the relationship in a Taiwanese sample. In both within- and between-culture analysis, we showed that the creative advantages of thinking paradoxically and experiencing conflict emerged among individuals who endorse lower (vs. higher) levels of middle ground (Study 2) and among Israelis whose culture predominantly endorses middle ground strategy less, but not among Singaporeans whose culture predominantly endorses middle ground more (Study 3). Study 4 further demonstrated the causal role of middle ground in the paradox-conflict-creativity link. To answer "why," Study 5 situationally induced integrative complex thinking that sets distinctions and forms syntheses among contradictory elements, and found that low endorsers of middle ground performed more creatively when they engaged integrative complex thinking to cope with paradoxes. This program of studies offers important insights on harnessing paradoxical experiences to catalyze creativity.
Attendance at emergency departments and unplanned hospital readmissions are common for frail older patients after discharge from hospitals. A virtual ward service was piloted to deliver ..."hospital-at-home" services by community nurses and geriatricians to frail older patients immediately after their discharge from hospital to reduce emergency services utilization.
This study examined the impacts of the virtual ward service on changes in the patients' emergency attendance and medical readmissions, and their quality of life (QOL).
A matched-control quasi-experimental study was conducted at four hospitals, with three providing the virtual ward service (intervention) and one providing the usual community nursing care (control). Subjects in the intervention group were those who are at high risk of readmission and who are supported by home carers recruited from the three hospitals providing the virtual ward service. Matched control patients were those recruited from the hospital providing usual care. Outcome measures include emergency attendance and medical readmission in the past 90 days as identified from medical records, and patient-reported QOL as measured by the modified Quality-of-Life Concerns in the End of Life Questionnaire (Chinese version). Wilcoxon signed-rank tests compared the changes in the outcome variables between groups.
A total of 39 patients in each of the two groups were recruited. The virtual ward group showed a greater significant reduction in the number of unplanned emergency hospital readmissions (-1.41±1.23 versus -0.77±1.31; P=0.049) and a significant improvement in their overall QOL (n=18; 0.60±0.56 versus 0.07±0.56; P=0.02), but there was no significant difference in the number of emergency attendances (-1.51±1.25 versus -1.08±1.48; P=0.29).
The study results support the effectiveness of the virtual ward service in reducing unplanned emergency medical readmissions and in improving the QOL in frail older patients after discharge.
In this trial of a recombinant VZV glycoprotein E subunit vaccine with the adjuvant AS01
B
, the risk of herpes zoster and postherpetic neuralgia is shown to be significantly lower in association ...with the vaccine than with placebo among persons 70 years of age or older.
Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) and typically manifests as a vesicular, painful dermatomal rash.
1
,
2
The most common complication of herpes zoster, postherpetic neuralgia, manifests as chronic neuropathic pain that can greatly limit daily activities.
1
,
3
–
6
The overall incidence of herpes zoster is 2.0 to 4.6 cases per 1000 person-years but increases with age to 10.0 to 12.8 per 1000 person-years among persons 80 years of age or older.
7
–
10
Similarly, the incidence of postherpetic neuralgia also increases with age.
10
–
13
Antiviral therapy can reduce the duration of herpes zoster rash . . .
Abstract
Background
Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities ...and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested.
Methods
Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (
n
= 46) and patients with bipolar disorder (
n
= 46) were compared against age-matched healthy controls (
n
= 46).
Results
Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect.
Conclusions
Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.